Evaluation of an Immersive Virtual Reality Safety Training Used to Teach Pedestrian Skills to Children With Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) are at an increased risk of injury, making safety skills training essential. Whether such training is conducted in the natural environment or in contrived settings is an important consideration for generalization and safety purposes. Immersive virtual reality (VR) environments may offer the advantages of both contrived and natural environment training settings, providing structure to create repeated learning opportunities in a safe and realistic analogue of the natural environment. The current study evaluated the effectiveness of an immersive VR safety skills training environment in teaching 3 children with ASD to identify whether it is safe to cross the street. After modifications to the VR training environment, all 3 participants reached mastery criteria in both VR and natural environment settings. Findings suggest that immersive VR is a promising medium for the delivery of safety skills training to individuals with ASD.

Identification and analysis of behavioral phenotypes in autism spectrum disorder via unsupervised machine learning.

BACKGROUND AND OBJECTIVE: Autism spectrum disorder (ASD) is a heterogeneous disorder. Research has explored potential ASD subgroups with preliminary evidence supporting the existence of behaviorally and genetically distinct subgroups; however, research has yet to leverage machine learning to identify phenotypes on a scale large enough to robustly examine treatment response across such subgroups. The purpose of the present study was to apply Gaussian Mixture Models and Hierarchical Clustering to identify behavioral phenotypes of ASD and examine treatment response across the learned phenotypes. MATERIALS AND METHODS: The present study included a sample of children with ASD (N = 2400), the largest of its kind to date. Unsupervised machine learning was applied to model ASD subgroups as well as their taxonomic relationships. Retrospective treatment data were available for a portion of the sample (n = 1034). Treatment response was examined within each subgroup via regression. RESULTS: The application of a Gaussian Mixture Model revealed 16 subgroups. Further examination of the subgroups through Hierarchical Agglomerative Clustering suggested 2 overlying behavioral phenotypes with unique deficit profiles each composed of subgroups that differed in severity of those deficits. Furthermore, differentiated response to treatment was found across subtypes, with a substantially higher amount of variance accounted for due to the homogenization effect of the clustering. DISCUSSION: The high amount of variance explained by the regression models indicates that clustering provides a basis for homogenization, and thus an opportunity to tailor treatment based on cluster memberships. These findings have significant implications on prognosis and targeted treatment of ASD, and pave the way for personalized intervention based on unsupervised machine learning.

An Evaluation of a Mobile Application Designed to Teach Receptive Language Skills to Children with Autism Spectrum Disorder.

The current study evaluated the effectiveness of a mobile application, Camp Discovery, designed to teach receptive language skills to children with autism spectrum disorder based on the principles of applied behavior analysis. Participants (N = 28) were randomly assigned to an immediate-treatment or a delayed-treatment control group. The treatment group made significant gains, p < .001, M = 58.1, SE = 7.54, following 4 weeks of interaction with the application as compared to the control group, M = 8.4, SE = 2.13. Secondary analyses revealed significant gains in the control group after using the application and maintenance of acquired skills in the treatment group after application usage was discontinued. Findings suggest that the application effectively teaches the targeted skills.

A Program Evaluation of Home and Center-Based Treatment for Autism Spectrum Disorder.

The present study aimed to retrospectively compare the relative rates of mastery of exemplars for individuals with ASD (N = 313) who received home-based and center-based services. A between-group analysis found that participants mastered significantly more exemplars per hour when receiving center-based services than home-based services. Likewise, a paired-sample analysis found that participants who received both home and center-based services had mastered 100 % more per hour while at the center than at home. These analyses indicated that participants demonstrated higher rates of learning during treatment that was provided in a center setting than in the participant's home.

Intensity and Learning Outcomes in the Treatment of Children With Autism Spectrum Disorder.

Ample research has shown that intensive applied behavior analysis (ABA) treatment produces robust outcomes for individuals with autism spectrum disorder (ASD); however, little is known about the relationship between treatment intensity and treatment outcomes. The current study was designed to evaluate this relationship. Participants included 726 children, ages 1.5 to 12 years old, receiving community-based behavioral intervention services. Results indicated a strong relationship between treatment intensity and mastery of learning objectives, where higher treatment intensity predicted greater progress. Specifically, 35% of the variance in mastery of learning objectives was accounted for by treatment hours using standard linear regression, and 60% of variance was accounted for using artificial neural networks. These results add to the existing support for higher intensity treatment for children with ASD.

An Evaluation of the Impact of Supervision Intensity, Supervisor Qualifications, and Caseload on Outcomes in the Treatment of Autism Spectrum Disorder.

Ample research has shown the benefits of intensive applied behavior analysis (ABA) treatment for autism spectrum disorder (ASD); research that investigates the role of treatment supervision, however, is limited. The present study examined the relationship between mastery of learning objectives and supervision hours, supervisor credentials, years of experience, and caseload in a large sample of children with ASD (N = 638). These data were retrieved from a large archival database of children with ASD receiving community-based ABA services. When analyzed together via a multiple linear regression, supervision hours and treatment hours accounted for only slightly more of the observed variance (r2 = 0.34) than treatment hours alone (r2 = 0.32), indicating that increased supervision hours do not dramatically increase the number of mastered learning objectives. In additional regression analyses, supervisor credentials were found to have a significant impact on the number of mastered learning objectives, wherein those receiving supervision from a Board Certified Behavior Analyst (BCBA) mastered significantly more learning objectives. Likewise, the years of experience as a clinical supervisor showed a small but significant impact on the mastery of learning objectives. A supervisor's caseload, however, was not a significant predictor of the number of learning objectives mastered. These findings provide guidance for best practice recommendations.

Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome.

Phelan-McDermid Syndrome (PMS), which is defined by a deletion within 22q13, demonstrates significant phenotypic variation. Given that six mitochondrial genes are located within 22q13, including complex I and IV genes, we hypothesize that mitochondrial complex activity abnormalities may explain phenotypic variation in PMS symptoms. Complex I, II, II + III and IV activity was measured in 51 PMS participants. Caretakers completed questionnaires and provided genetic information through the PMS foundation registry. Complex activity was abnormal in 59% of PMS participants. Abnormalities were found in complex I and IV but not complex II + III and II activity, consistent with disruption of genes within the 22q13 region. However, complex activity abnormalities were not related to specific gene deletions suggesting a "neighboring effect" of regional deletions on adjacent gene expression. A specific combination of symptoms (autism spectrum disorder, developmental regression, failure-to-thrive, exercise intolerance/fatigue) was associated with complex activity abnormalities. 64% of 106 individuals in the PMS foundation registry who did not have complex activity measured also endorsed this pattern of symptoms. These data suggest that mitochondrial abnormalities, specifically abnormalities in complex I and IV activity, may explain some phenotypic variation in PMS individuals. These results point to novel pathophysiology mechanisms and treatment targets for PMS patients.

Early Screening of Autism Spectrum Disorder: Recommendations for Practice and Research.

This article reviews current evidence for autism spectrum disorder (ASD) screening based on peer-reviewed articles published to December 2013. Screening provides a standardized process to ensure that children are systematically monitored for early signs of ASD to promote earlier diagnosis. The current review indicates that screening in children aged 18 to 24 months can assist in early detection, consistent with current American Academy of Pediatrics' recommendations. We identify ASD-specific and broadband screening tools that have been evaluated in large community samples which show particular promise in terms of accurate classification and clinical utility. We also suggest strategies to help overcome challenges to implementing ASD screening in community practice, as well as priorities for future research.

Early Identification of Autism Spectrum Disorder: Recommendations for Practice and Research.

Early identification of autism spectrum disorder (ASD) is essential to ensure that children can access specialized evidence-based interventions that can help to optimize long-term outcomes. Early identification also helps shorten the stressful "diagnostic odyssey" that many families experience before diagnosis. There have been important advances in research into the early development of ASDs, incorporating prospective designs and new technologies aimed at more precisely delineating the early emergence of ASD. Thus, an updated review of the state of the science of early identification of ASD was needed to inform best practice. These issues were the focus of a multidisciplinary panel of clinical practitioners and researchers who completed a literature review and reached consensus on current evidence addressing the question "What are the earliest signs and symptoms of ASD in children aged ≤24 months that can be used for early identification?" Summary statements address current knowledge on early signs of ASD, potential contributions and limitations of prospective research with high-risk infants, and priorities for promoting the incorporation of this knowledge into clinical practice and future research.

Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research.

This article reviews current evidence for autism spectrum disorder (ASD) interventions for children aged <3 years, based on peer-reviewed articles published up to December 2013. Several groups have adapted treatments initially designed for older, preschool-aged children with ASD, integrating best practice in behavioral teaching methods into a developmental framework based on current scientific understanding of how infants and toddlers learn. The central role of parents has been emphasized, and interventions are designed to incorporate learning opportunities into everyday activities, capitalize on "teachable moments," and facilitate the generalization of skills beyond the familiar home setting. Our review identified several comprehensive and targeted treatment models with evidence of clear benefits. Although some trials were limited to 8- to 12-week outcome data, enhanced outcomes associated with some interventions were evaluated over periods as long as 2 years. Based on this review, recommendations are proposed for clinical practice and future research.

Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders.

Hyperbaric oxygen therapy (HBOT) has been used to treat individuals with autism. However, few studies of its effectiveness have been completed. The current study examined the effects of 40 HBOT sessions at 24% oxygen at 1.3 ATA on 11 topographies of directly observed behavior. Five replications of multiple baselines were completed across a total of 16 participants with autism spectrum disorders. No consistent effects were observed across any group or within any individual participant, demonstrating that HBOT was not an effective treatment for the participants in this study. This study represents the first relatively large-scale controlled study evaluating the effects of HBOT at the level of the individual participant, on a wide array of behaviors.

Pyrosequencing study of fecal microflora of autistic and control children.

There is evidence of genetic predisposition to autism, but the percent of autistic subjects with this background is unknown. It is clear that other factors, such as environmental influences, may play a role in this disease. In the present study, we have examined the fecal microbial flora of 33 subjects with various severities of autism with gastrointestinal symptoms, 7 siblings not showing autistic symptoms (sibling controls) and eight non-sibling control subjects, using the bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP) procedure. The results provide us with information on the microflora of stools of young children and a compelling picture of unique fecal microflora of children with autism with gastrointestinal symptomatology. Differences based upon maximum observed and maximum predicted operational taxonomic units were statistically significant when comparing autistic and control subjects with p-values ranging from <0.001 to 0.009 using both parametric and non-parametric estimators. At the phylum level, Bacteroidetes and Firmicutes showed the most difference between groups of varying severities of autism. Bacteroidetes was found at high levels in the severely autistic group, while Firmicutes were more predominant in the control group. Smaller, but significant, differences also occurred in the Actinobacterium and Proteobacterium phyla. Desulfovibrio species and Bacteroides vulgatus are present in significantly higher numbers in stools of severely autistic children than in controls. If the unique microbial flora is found to be a causative or consequent factor in this type of autism, it may have implications with regard to a specific diagnostic test, its epidemiology, and for treatment and prevention.

Urinary porphyrin excretion in neurotypical and autistic children.

BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU). OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism. METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism. RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received. CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.

Retrospective analysis of clinical records in 38 cases of recovery from autism.

BACKGROUND: Twenty years of research on early intensive treatment using applied behavior analysis (ABA) for children with autism has consistently produced robust effects. There appears to be a subset of children whose response to intensive ABA treatments includes achieving a level of functioning that is indistinguishable from typically developing peers. The purpose of this study was to describe a subset of children who recovered from autism following intensive ABA interventions. METHODS: We reviewed the clinical files of 38 children with autism who achieved an optimal outcome after receiving intensive ABA services. RESULTS: The mean age at intake was 40 months. Average IQ was 83.6 at intake and 107.9 at discharge. Mean adaptive skills were 68.04 at intake and 88.87 at discharge. CONCLUSIONS: Our study corroborates the finding that some children with autism who receive early intensive behavioral intervention achieve functioning in the average range.

Applied behavior analytic interventions for children with autism: a description and review of treatment research.

BACKGROUND: Autism is a disorder characterized by pervasive delays in the development of language and socialization, and the presence of stereotyped, repetitive behaviors or nonfunctional interests. Although a multitude of treatments for autism exist, very few have been the subject of scientific research. The only treatment that has been supported by substantial empirical research is treatment based on applied behavior analysis (ABA). METHODS: This article describes components of comprehensive ABA treatment programs, reviews research on effectiveness, and discusses issues related to collaboration between ABA and psychiatry. RESULTS: ABA has been supported by several hundred single case experiments and an increasing number of between-groups studies. Comprehensive ABA treatment programs are comprised of multiple intervention procedures, such as discrete trial instruction and natural environment training, and are founded on basic principles of learning and motivation, such as positive reinforcement, extinction, stimulus control, and generalization. Clinicians in the fields of ABA and psychiatry have similar goals regarding client outcome, and several ABA measurement and analysis procedures produce information that may be useful to psychiatrists. CONCLUSIONS: ABA treatment programs for individuals with autism are supported by a significant amount of scientific evidence and are therefore recommended for use. Patient care would likely benefit from a greater degree of collaboration between practitioners in the fields of ABA and psychiatry.

Comparison of data-collection methods in a behavioral intervention program for children with pervasive developmental disorders: a replication.

Cummings and Carr (2009) compared two methods of data collection in a behavioral intervention program for children with pervasive developmental disorders: collecting data on all trials versus only the first trial in a session. Results showed that basing a child's progress on first-trial data resulted in identifying mastery-level responding slightly sooner, whereas determining mastery based on all trials resulted in slightly better skill maintenance. In the current replication, no such differences in indication of mastery or maintenance were observed when data were collected on all trials or the first trial.

Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15.

Although many articles have reported immune abnormalities in autism, NK cell activity has only been examined in one study of 31 patients, of whom 12 were found to have reduced NK activity. The mechanism behind this low NK cell activity was not explored. For this reason, we explored the measurement of NK cell activity in 1027 blood samples from autistic children obtained from ten clinics and compared the results to 113 healthy controls. This counting of NK cells and the measurement of their lytic activity enabled us to express the NK cell activity/100 cells. At the cutoff of 15-50 LU we found that NK cell activity was low in 41-81% of the patients from the different clinics. This NK cell activity below 15 LU was found in only 8% of healthy subjects (p<0.001). Low NK cell activity in both groups did not correlate with percentage and absolute number of CD16(+)/CD56(+) cells. When the NK cytotoxic activity was expressed based on activity/100 CD16(+)/CD56(+) cells, several patients who had displayed NK cell activity below 15 LU exhibited normal NK cell activity. Overall, after this correction factor, 45% of the children with autism still exhibited low NK cell activity, correlating with the intracellular level of glutathione. Finally, we cultured lymphocytes of patients with low or high NK cell activity/cell with or without glutathione, IL-2 and IL-15. The induction of NK cell activity by IL-2, IL-15 and glutathione was more pronounced in a subgroup with very low NK cell activity. We conclude that that 45% of a subgroup of children with autism suffers from low NK cell activity, and that low intracellular levels of glutathione, IL-2 and IL-15 may be responsible.

Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders.

Multiple studies now demonstrate that autism is medically characterized, in part, by immune system dysregulation, including evidence of neuroglial activation and gastrointestinal inflammation. This neuroglial process has further been characterized as neuroinflammation. In addition, a subset of autistic children exhibit higher than average levels of androgens. Spironolactone is an aldosterone antagonist and potassium-sparing diuretic with a desirable safety profile. It possesses potent anti-inflammatory and immune modifying properties that might make it an excellent medical intervention for autism spectrum disorders. Furthermore, spironolactone demonstrates substantial anti-androgen properties that might further enhance its appeal in autism, particularly in a definable subset of hyperandrogenic autistic children. One case report is briefly reviewed demonstrating objective clinical improvements in an autistic child after spironolactone administration. Additional research in controlled trials is now needed to further define the risks and benefits of spironolactone use in children with autism.